CRAC CHANNEL INHIBITOR
Program Overview
Ion channels are pipes in cell membranes that provide for and regulate the flow of ions – positively or negatively charged molecules – in and out of cells. They are critical for the essential functioning of many cell types.
As one example, ion channels play a critical role in the ability of electrically excitable cells, such as neurons or muscle cells, to discharge. Drugs that modulate ion channels on excitable cells have proven to be a very successful therapeutic category, with dozens of such drugs on the market and commonly prescribed for the treatment of various neurological and cardiovascular disorders.
Synta has exclusive ownership of a portfolio of intellectual property and promising drug candidates targeting novel ion channels on non-excitable cells, such as cells from the immune system. Ion channels on non-excitable cells can play an important role in certain cell signaling pathways. Because these channels are often very specific to certain tissue or cell types, and their role is critical to the functioning of those cells or tissues, ion channel modulators offer the potential for highly targeted action to improve a disease state.
Synta’s ion channel modulators block calcium entry into immune cells. By doing so, these drug candidates inhibit cytokine release, T cell activation, and immune cell proliferation. These compounds form the basis for a new class of drug candidates for treating asthma, transplant rejection, allergies, cancer, and other conditions.
See additional reference on ion channels.
CRAC Channel
Our lead compound series includes a highly potent inhibitor of the critical channel in immune cell signaling known as the CRAC (Calcium Release - Activated Calcium) channel, and has shown potent anti-inflammatory activity in preclinical models. CRAC channels are critical to the activation of T-lymphocytes, mast cells and other hematopoietic cells, as they provide the primary route for calcium entry, which drives multiple cell signaling processes. CRAC inhibitors would be a promising new drug category for the treatment of several diseases including graft-versus-host disease (GVHD), immune disorders, allergies, and asthma. The Synta compounds, which have demonstrated highly potent inhibition of cytokine production (including IL-2 and TNFa), appear to offer the most potent and selective CRAC inhibition seen to date.
Preclinical Data
Our CRAC inhibitors have shown potent anti-inflammatory activity in preclinical models. Data have demonstrated that inhibition of both IL-2 and TNFa with our CRAC inhibitor is comparable to or better than cyclosporin, a commonly used medication designed to suppress the immune system.
Development Status
Animal studies are ongoing to optimize the safety, pharmacokinetics, and efficacy of these molecules in disease models. |
